Role of free fatty acids in hepatic insulin resistance during late pregnancy in conscious rabbits
Gilbert, M.; Pere, M.C.; Baudelin, A.; Battaglia, F.C.
American Journal of Physiology 260(6 Pt 1): E938-E945
1991
ISSN/ISBN: 0002-9513 PMID: 2058668 Document Number: 386674
This study addresses whether elevated free fatty acids (FFA) contribute to the hepatic insulin resistance of pegnancy. We applied a euglycemic hyperinsulinenic clamp with or without. Intralipid plus heparan infusion in conscious virgin and pregnant rabbits after an 18-h fast coupled with chronic catheterization of the hepatic acid portal veins and femoral artery. A primed constant infusion of [3-3H]glucose was used to determine glucose fluxes. Insulin was infused into a mesenteric vein for 140 min. In pregnant rabbits, basal net hepatic uptake of lactate was almost two times of non-pregnant rabbits. During a euglycemic hyperinsulinemic clamp there was a decline of .apprx. 65% in hepatic lactate uptake in nonpregnant rabbits at 80 min, whereas a smilar decrease was observed only at 40 min in pregnant rabbits. The effect was blocked by lipid infusion. In the basal state the hepatic uptake of FFA was greater in pregnant than in nonpregnant animals. During the hyperinsulinemic clamp the hepatic uptake dropped by .apprx. 70 and .apprx. 30% in nonpregnant and pregnant females, respectively. Lipid infusion did not prevent the hepatic FFA uptake and hepatic ketone body output from decreasing. Hepatic glucose production was totally suppressed in the control period in nonpregnant animals but not during lipid infusion (.apprx. 65%). Hepatic glucose production was not significantly different between pregnant and nonpregnant rabbits during lipid infusion. Glucose utilization was markedly reduced in nonpregnant animals during lipid infusion to levels comparable with that in pregnant animals. We conclude that acute elevation in FFA levels in nonpregnant rabbits simulates two aspects of insulin resistance observed in late pregnancy: 1) it induces impairment in suppressibility of hepatic glucose production, and 2) it inhibits glucose utilization.